The complicated news from MSK as of the end of January 2019

The prologue:   

MSK gave me a prognosis for the first time, when we met with our oncologist on Thursday, January 24, 2019. The prognosis is six months.

The reasons:

I had been having difficulties. A scan back on December 11, 2018 had determined that my cancer was again in action. Shaping a response to that took time, both because of the holiday season and because I’m sure the doctors wanted to be as careful as possible. The conclusion they seemed to be coming to, even before we met on January 24, was that there were no good affirmative treatments likely to be available. We had no doubt this was a reasonable assessment of the situation, but felt that it might still be true that even a treatment unlikely to succeed was better than no treatment at all. Our oncologist’s view was, we thought, evolving to the opposite perspective: that if no treatment was likely to be successful then there was no point in trying them at all.

What decided the issue was a series of scans in late January, which included a January 15 X-ray of my abdomen as well as a CT scan, that same day, of my abdomen and pelvis done during my digestive blockage visit to MSK’s Urgent Care ward (a visit I blogged about as well). They also included an MRI of my pelvis on January 22. I had yet another scan on January 25, but that was to diagnose whether I had suffered a broken foot or not, and didn’t otherwise contribute to the study of my condition.

In truth, the information in theses scans is hard to keep clear and distinct. One scan is referred to as comparing its findings with data from a scan done a couple of days later, but I had no such additional scan that day. Another scan attributes the wrong disease to me – saying I have colon cancer when I actually have a different illness, cholangiocarcinoma. These mistakes are a bit unsettling, but the general import of the scan results nevertheless emerges clearly.

If the scans proved determinative, what led MSK to determine that they should do the scans in the first place? Their concerns were triggered in good part by the MSK physicians’ growing suspicion about a lesion, a damaged area, in my right iliac bone, which is part of the pelvis. MSK had been aware of this spot since approximately April 2018, but had not been particularly suspicious about it. Now, however, yet another scan in December 2018 had shown growth in this spot, and growth is important. For our part, we too had hoped not to need to pay attention to this spot. After all, I didn’t think I had any symptoms of it at all – but over the weekend before the scan I began to realize that maybe I did have symptoms, perhaps from walking further than was comfortable, perhaps from such minor motions as bending over to do the dishes. Mostly not a lot of pain – but cholangiocarcinoma is full of minor, yet ultimately meaningful, symptoms. Meanwhile, growth is cancer’s specialty, so the fact that this spot had recently started to grow was a bad sign.

The scan series in January 2019 appears to have confirmed two thoughts for our oncologist. The first is that the cancer has escaped from the liver and reached the bones as well. One report, on still another CT scan done on January 15, 2019, indicated this but not elaborately; a second, on an MRI scan done a week later, January 22, 2019, left no room for doubt. There has been a lot of damage to the bones of the pelvic area, presumably the result of its infiltration by the cancer, and all of it appears to have taken place in the last 12 months. Parts of the bone have probably died. All of this makes me vulnerable to things like bone fractures, including hip fractures, which would put me right away in a wheelchair.  

When the skeleton weakens, you are at greater risk both for “spontaneous” fractures, which can apparently take place while you’re doing nothing more strenuous than sleeping, and for fractures caused by impact and accident. There are things that can be done to reduce the chances of incident, such as installing assistive equipment, like guide bars, machinery to help me get around the house; as we do more with this I may blog about our progress, but in any case this effort is now underway.

As to the impact and accident fractures, for me those are more likely than they otherwise might be because of all the water I’m still retaining, especially in my feet. The water retention is another impact of my damaged liver (and of its interaction with the diuretic medication, and in turn with my kidneys). The water retention in itself isn’t a big problem, and doesn’t contribute to my underlying cancer in any direct way. However, in the Department of Irony, currently running strong, a couple of hours after we got home from our Thursday meeting last week with the oncologist, at which we’d received a lot of precautionary guidance, I fell at the bottom of our stairs. Fortunately the fall was only two steps down. I landed hard, but even more fortunately the fall didn’t fracture anything; it caused “just” a sprain. My left foot did take on some remarkable colors right away. Depending on how many separate sprains I gave myself, recovery could take as long as six or seven weeks. So far, however, things seem to be moving quite quickly and positively.

The second conclusion our oncologist and her colleagues have reached is that my liver has already been seriously damaged. One measure of such damage is the growth of the cancer itself, and the January 15 CT scan of my abdomen and pelvis lists a number of growing, and probably new, changes in my liver and bile duct of this sort. Other evidence comes from blood testing of liver function. My general sense is that my liver and kidney blood numbers were good until the conclusion of the high-intensity radiation treatment this past summer, and that at that point they began to deteriorate. It’s easy to see what caused the damage: not the water retention, but rather the combination of three years of different powerful treatments, including chemotherapy and, most recently, high-intensity radiation. These all did their job, staving off or pushing back the cancer for years – the oncologist has been happy to have me as an “outlier” to the normal course of the disease – but the price was liver damage. I’ve recently read that actually the liver handled over 500 different functions in the body, not just the 400 I’d seen referred to earlier. Any of those may now be malfunctioning.

What’s bad about liver damage is that there is no cure for it. It is possible for the liver to regenerate, but that is a slow process and one under nature’s guidance; there seems to be little if anything a doctor can do to bring about regeneration by direct medical intervention. There is no “liver-all” pill to take 3 times a day! The only method available to doctors of which I’m aware is resection – the complete surgical removal of part of the liver, but MSK has never seen me as a good candidate for this approach. That means that any heavy-duty treatment that gets applied at this point runs the risk of deepening my current liver problems, and if the liver stops functioning, that is really the end.

What is to be done next?

That in turn suggests that what’s ideal for me is to stick with exactly what I now have. The status quo has its inconveniences, such as water retention, but they can all be managed. Evidently, however, our oncologist anticipates a continued deterioration of the liver, presumably as a result of a continued growth of my cancer.

To stave that off as long as possible therefore becomes our next goal. Happily, there is something that can be done about this: the application of low-intensity radiation. High-intensity beams are too powerful and too dangerous, but low-intensity beams have been in use for a number of years and their capacity to slow, though not end, expansion of the cancer in the bones (and perhaps even in the liver itself – a point I want to ask more about) is evidently well-established.

One other point: I exaggerated a bit when I said that MSK took the view that there was nothing truly affirmative to be done. There is one treatment available which, though not very promising for patients with my kind of cancer (it wasn’t designed with this illness in mind), still could conceivably help and even help a lot: Keytruda. This is the drug that helped Jimmy Carter fight off brain cancer. MSK is comfortable with trying it because they feel they know very well what its potential downsides in the body are, and they’re mild. So they are quite confident that Keytruda won’t undermine what’s left of my liver functioning, and though it likely won’t improve matters either, it will succeed or fail without further weakening me.

The only problem with Keytruda is that it is very expensive – I think over $10,000 for each treatment, with the treatments every three weeks. Merck, which makes Keytruda, enables many potential patients to get around this problem by giving them access to the drug as a “compassionate use” under federal law; no doubt this is only partly an act of charity, while also serving as a way for Merck to continue gathering data on its drug, with a view to the widest possible use and sale of the medication. In any case, we and MSK have applied to receive the drug as a compassionate use. Decisionmaking at Merck this month has apparently been slow, for reasons no one outside the company is sure of, but we will continue to press the point.

There may be other possibilities, though with the difficulties my liver and kidneys now face I may not easily be able to qualify for most experimental trials. Even if I can qualify, we’ll have to determine whether these experiments make sense for me. For example, we’ve certainly considered the “CAR-T” experiment at the National Institutes of Health, a trial in which the patient’s immune system is more or less entirely removed, re-trained to focus on cholangiocarcinoma, and then returned to the patient’s body. The general sense Teresa and I have is that steps like these are a last resort, or no resort at all, because they do pose serious risks of danger to the patient – especially, we assume, one with a damaged liver already.

And meanwhile:

I plan to live the life I’ve lived, valuing and spending time with my family and friends. I also plan to continue the final steps in the work that I’ve had underway, the biography of my late South African friend Arthur Chaskalson, roughly since I received my diagnosis in 2015. I’ve often felt since I became ill that each day in itself is a wonderful thing. In recent months my sense of this has wobbled at times, so now I mean to remind myself, and to take joy in each remaining day. And if there turn out to be a lot of those remaining days, so much the better!

                                                                                                                 

Latest news -- back to the fight

Teresa and I spent yesterday at Memorial Sloan Kettering. Unfortunately we didn't come home with news as good as we had gotten from other recent sessions there.

The short version is this: they found from a CT scan on Tuesday, December 11, 2018 that a few tumors in my liver which had been quiet have now woken up and grown a little (roughly a centimeter in each case). Meanwhile a very small lesion in my iliac bone (a “lesion” is a damaged area, and the iliac is the largest bone of the pelvis), which they’ve been aware of but have never seen any clear indication of malignancy from, has also grown a little, which raises a substantial possibility that this is a metastasis (a spread) outside the liver.

What to do? Well, we intend to fight the disease, which is the strategy that has served us pretty well up to now. But it’s harder, because we’ve already used most or all of the proven strategies. (Though perhaps not all; we may talk with the doctor who administered the radiation this summer, for instance, in case he sees something our oncologist – who was out during our appointment yesterday with a respiratory illness, so we only really dealt with her nurses – did not.) Assuming we’ve tried everything proven that Sloan Kettering offers, we might actually sit tight, not getting treatment. This would not be because we’re giving up, but rather because if the tumors in question are growing relatively slowly, then for my case (somewhat as in many cases of men with prostate cancer) it can actually make sense to be equally patient – while we wait for researchers and clinicians to invent the next treatment that really works.

Or we may try experimental treatment ourselves. Experiments, in the form of clinical trials, are the process by which those treatments that really work are found and developed. Getting a treatment that is currently unproven won't accomplish much if it turns out the treatment really doesn't work. But joining the trial means that you potentially get access to the latest possible approaches earlier than other people do, and if they work you get your treatment before most of the world. 

One especially attractive example of this would be the drug Keytruda, which you might remember successfully pushed back Jimmy Carter’s brain cancer. Keytruda is an immunotherapy drug, and it helps to have the right mutations for Keytruda and other similar immunotherapy drugs to target. So far it doesn’t seem that I have any particularly “targetable” or “actionable” mutations. But some people benefit from these drugs even without having the mutations at which they were originally aimed. The biggest problem with Keytruda, aside from the fact that it certainly doesn’t always work, is that it is expensive, unless they (Merck is the manufacturer) give it to you as a compassionate gesture. That they often do, and we applied for it yesterday.

A second place for experimental treatment is in other treatments being tried inside Sloan Kettering itself. MSK evidently has two sets of first-round (i.e. very tentative) clinical trials going on. One set involves immunotherapy (that is, treatment aimed -- like Keytruda -- at the targetable mutations that I seem to be short of, but that perhaps aren’t essential to the success of treatment). The second set involves, I guess, other  experiments. It looks like we’ll be finding out more about these in the next two or three weeks.

The third place for experimental treatment is, as you’d guess, in other treatments besides Keytruda that are being developed outside Sloan Kettering. Different institutions are running their own trials. There’s a possibly promising one at M.D. Anderson in Houston; another at the National Institutes of Health in DC; and Teresa is applying her formidable web research skills to locating others that show some promise.  

So that’s the situation. I intend to work hard on finishing the 400,000 word version of my book (and if I can also produce a shorter version, more suitable for trade publication, so much the better); look forward to spending time with family and friends; and, as I said, Teresa and I plan to keep on fighting.  

A new tumor -- and what to do about it

So we've seen our oncologist and she’s given us the report on last week’s MRI. It's not what we'd hoped for but fortunately there's lots we can do about it.

The MRI confirms that the new growth in my liver is cancer. This immediately opens up the kinds of questions I sketched out in last post, which begin with "why is this tumor growing while the others are staying stable or getting smaller?" The contrast is if anything sharper than we'd realized: all the old tumors have, in aggregate, reduced in size by 35 %, while this one has been growing. (One question is whether this one has actually been growing as fast as it seems; it's possible that if they look back at older scans, as they plan to, they'll find that this one has been around, lurking, for some time.) We have the sense that our oncologist finds this quite unusual, and she’s said she wants to be as creative as possible in shaping a response. With that in mind, the first thing she did was to present my case to the full treatment team the day after she met with us (more on what the team recommended in a moment).

Basically there seem to be two possible answers to the "why is this tumor different" question. One is that for some reason the chemo that's been going to the liver and doing quite well with the other tumors has missed this one. That could be because the chemotherapy all comes into the liver via just one blood vessel (I used to have two, but they had to close one off when they did the surgery to install the pump that sends chemotherapy directly into the liver), and possibly something about its flow from that blood vessel to the other tumors and the rest of the liver causes it to miss this one. They can check this with what’s called a “pump study,” and after my case was presented to the whole treatment team last week, they decided to move very quickly to get that done – in fact, I had the pump study this afternoon. (That was quite an experience – they use radioactive injections whose progress inside the body is followed mainly by gigantic “gamma cameras,” and I’m radioactive for the next 4 days!) If it turns out that somehow the chemotherapy is missing this new tumor, then there may be something they can do to reroute it.  

The other possible answer to the "why is this tumor different" question is that the tumor itself is intrinsically different. In particular, the new tumor may have a different genetic make-up than the others, the result of some new mutations in my cancer cells. Evidently cancer is extremely clever about mutating in the face of attack. One way to test this possibility is to do a biopsy of the tumor itself, and they're discussing this. But, I think because the bile ducts and blood system are so intermingled, evidently it's quite likely that DNA from the new tumor is actually present now in my blood, so last week they took blood to send off to a company that will test the tumor's genetic makeup by using just my blood. That should tell us something, in particular about the possibility of immunotherapy targeted at whatever new mutations turn out to be present.

Meanwhile, we wait, though only for a few days. So far our oncologist seems to feel that the pump chemotherapy, using the drug FUDR and focused just on the liver, is working well – except for this new tumor – while the whole-system chemotherapy, using gemcitabine, has come up short. This isn't totally surprising; I've been on gemcitabine since December 2015, and these drugs' impact tends to diminish over time. It sounds like our oncologist is thinking about another systemic drug, related to the pump drug, perhaps one called 5FU (nice name). But it seems they want to know what the pump study shows before making decisions about my medication.

In the somewhat longer run, the oncologist had me sign up last week for the "patient assistance program" run by the giant drug company Merck for its drug Keytruda. Keytruda is an immunotherapy drug that apparently can be tried regardless of whether my tumors, or some of them, have particularly promising mutations to target. The patient assistance program will, we hope, reduce the cost of the drug, perhaps down to zero – which would be a lot less than its list price, which seems to be about $15,000 every three weeks! Realistically, that means that the drug would otherwise probably only be available via some new clinical trial, so the patient assistance program is an attractive possibility for down the road – though I think they’ll try modifying the chemotherapy prescription first. They may also try targeting this new tumor by itself by methods they haven't yet used, such as implanted radioactive pellets or various other ways of attacking an individual tumor. Till now, they haven’t used these individual targeting approaches with my tumors, though I did have one that was much larger than the rest. So why now? Our impression is that they may feel it makes more sense to attack this new tumor individually than it did to attack any one of my pre-existing tumors, precisely because this new one appears to be different from the rest.

All in all, Teresa and I agree that it would be better not to have wound up with a case that’s so clinically interesting. But we also agree that, since that’s what I have, it is really good to have Sloan Kettering's collective experience and expertise being brought to bear on it!